Immunometabolic predictive factors in Merkel cell carcinoma (MCC) patients treated with avelumab.
Authors: Giuseppe Badalamenti, Lorena Incorvaia, Laura Algeri, Ignazio Ugo Carreca, Chiara Brando, Giorgio Madonia, Marta Peri, Alessandra Cucinella, Alessandro Perez, Nadia Barraco, Tancredi Didier Bazan Russo, Federica Li Pomi, Anna Paola Carreca, Valerio Gristina, Antonio Galvano, Juan Iovanna, Daniele Fanale, Viviana Bazan, Antonio Russo, Ignazio Ugo Carreca
Journal: Journal of Clinical Oncology (2022)

e21525 Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The link between MCC and immune suppression is well demonstrated. The population of patients with MCC is frequently elderly and frail, making it essential to determine whether the results of clinical trial can be replicated in a real-world setting. Despite the introduction of immune-checkpoint inhibitors (ICIs) has provided great benefit for some patients with advanced MCC (aMCC), it remains a subsets of patients who are refractory to ICIs or develop acquired resistance over time. Thus, there is a clinical need for predictive factors of ICI response. Methods: Twenty patients with aMCC treated with avelumab were included. The treatment was administered as I or II line. Clinical-pathological characteristics, Body Mass Index (BMI), and response to avelumab were analyzed from a MCC System database prospectively collected. An explorative analysis was performed, for available samples, to investigate: i) the plasma levels of soluble PD-1 (sPD-1), and PD-L1 (sPD-L1) collected at baseline, measured using homemade ELISA assays not yet commercially available, and designed according to investigator specifications; ii) IHC for PD-L1 in tumor samples; iii) the presence/absence/class (brisk vs no-brisk) of tumor-infiltrating lymphocytes (TILs) in tumor samples. The primary outcome investigated was the Time to Treatment Failure (TTF). Results: From February 2019 to January 2022, twenty (20) patients were included in the study. The median age was 74 (range 56-83); 10 patients were men (50%) and 10 were women (50%). Seventeen (17) patients (85%) were treated with avelumab as I line, and 3 patients (15%) as II line. The overall response rate was 65% (70.6% in I line patients). One (1) patient (5%) had a complete response (CR), 13 patients (65%) partial response (RP), 4 patients (20%) stable disease (SD), and 2 patients (10%) had a progression disease (PD). Overall median TTF was 22 months (95% confidence interval [CI]: -13.0-30.9). At the time of data analyses, a total of 9 events (progression or death) occurred (45%). Notably, a BMI ≥ 30 was significantly associated with longer TTF (p = 0.004) and objective response rate (p = 0.01). In the explorative biomarker analysis, preliminary data on 6 tumor and plasma samples, showed that plasma sPD-1 &gt; 3.8 ng/ml, and the presence of PD-L1 and brisk TILs on tumor samples, were associated to longer TTF. Conclusions: These finding highlight the complex immune-metabolic interplay in the immunotherapy response. These data extends the previous finding on “obesity paradox” and the role of BMI as predictive factors of ICIs. The data on biomarker analysis warrants further prospective validation.